Drug-coated balloons in coronary in-stent restenosis: a systematic review and meta-analysis comparing sirolimus and biolimus with paclitaxel platforms

Background Coronary in-stent restenosis (ISR) remains a relevant clinical challenge despite advances in drug-eluting stent technology. Drug-coated balloons (DCBs) offer a metal-free revascularization option, with microtubule stabilizer drug – paclitaxel coated balloons (PCBs) being the most validated. The m-TOR inhibitors drugs like Sirolimus and Biolimus coated balloons (SCBs, BCBs) have emerged as alternatives, but comparative efficacy and safety remain uncertain. Objective To compare the efficacy and safety of SCBs and BCBs with PCBs in the treatment of coronary ISR. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted according to PRISMA guidelines. Multiple databases were searched through February 2025 for RCTs comparing SCB or BCB with PCB in ISR. The primary outcome was target lesion revascularization (TLR). Secondary outcomes included mortality, target vessel myocardial infarction (TVMI), binary restenosis, late lumen loss (LLL), percentage diameter stenosis, and minimal lumen diameter (MLD). Results Six RCTs involving total of 988 patients with coronary ISR (due to DES n = 887 and BMS n = 92) were analyzed. SCB/BCB use was associated with a non-significant trend toward higher TLR (RR = 1.24, 95% CI 0.91–1.69) compared with PCB. No significant differences were observed for mortality, TVMI, binary restenosis, LLL, diameter stenosis, or MLD, even upon subgroup analysis based on type of drug coated balloon used and etiology of ISR (DES-ISR or DES + BMS-ISR). Conclusion Our study finds that SCBs and BCBs are non-inferior to PCBs in treatment of coronary ISR in terms of safety and efficacy, though criteria for selection of type of balloon to be utilized could not be derived as studies included had comparable baseline characteristics and subgroup analysis did not reveal any difference in results as well. However, given the limited number of direct comparisons, low certainty of evidence for many outcomes, and a numerically higher trend for TLR in the SCB/BCB group, a definitive conclusion of equivalence cannot be drawn, and further research is warranted.